Searching for the neural basis of reserve against memory decline: intellectual enrichment linked to larger hippocampal volume in multiple sclerosis.

BACKGROUND AND PURPOSE: Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds 'reserve' against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated. METHODS: Relapse-onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97). RESULTS: Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (r(p) = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume. CONCLUSIONS: These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience-dependent neuroplasticity within the hippocampus.

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Diagnosis concealment is prevalent in MS, and associated with diagnosis experience.

BACKGROUND: Receiving a diagnosis of multiple sclerosis (MS) can be stressful; later, patients may conceal their diagnosis. Here, we aimed to (1) assess prevalence of disclosure and concealment behaviors, and (2) explore whether diagnosis experience is associated with later concealment and if MS provider engagement on this topic modifies concealment. METHODS: In a survey-based study, MS patients completed DISCO-MS assessing disclosure and concealment and responded to questions about diagnosis experience and practitioner attention to disclosure. Frequency analysis and Pearson's correlations were used in exploratory analyses. RESULTS: 428 adults with MS participated. 49% (N = 201) conceal their diagnosis. Higher education [t(405) = 3.66, p < 0.001], younger age (r = -0.15, p = 0.002), and shorter disease duration (r = -0.18, p = 0.010) were associated with higher concealment. 39% (N = 159) anticipate negative consequences of disclosure. Individuals reporting positive diagnosis experience (26%, N = 102) were less likely to conceal later in disease course compared to those with negative experience (34%, N = 136) [t(233) = 2.483, p = 0.014]. Patients whose MS providers discussed disclosure (23%, N = 73) anticipated less negative consequences of disclosure [t(323) = 2.475, p = 0.014]. CONCLUSIONS: Diagnosis concealment is common in MS. Favorable diagnosis experience and provider attention to the topic of disclosure throughout the MS disease course may influence diagnosis concealment.

Elevated body temperature is linked to fatigue in an Italian sample of relapsing-remitting multiple sclerosis patients.

Elevated body temperature was recently reported for the first time in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls. In addition, warmer body temperature was associated with worse fatigue. These findings are highly novel, may indicate a novel pathophysiology for MS fatigue, and therefore warrant replication in a geographically separate sample. Here, we investigated body temperature and its association to fatigue in an Italian sample of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with our original report, we found elevated body temperature in the RRMS sample compared to healthy controls. Warmer body temperature was associated with worse fatigue, thereby supporting the notion of endogenous temperature elevations in patients with RRMS as a novel pathophysiological factor underlying fatigue. Our findings highlight a paradigm shift in our understanding of the effect of heat in RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although randomized controlled trials of cooling treatments (i.e., aspirin, cooling garments) to reduce fatigue in RRMS have been successful, consideration of endogenously elevated body temperature as the underlying target will enhance our development of novel treatments.